OBJECTIVETo determine the prevalence of a common GJB2 mutation in a big Chinese population of deaf children and the features of its distribution in regions all over the nation and to provide epidemiology data and expertise for genetic testing of deafness in China.

METHODSThe DNA samples of NSHI patients and normal controls were collected from different typical areas of China. The method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with ApaI was used to determine the genotype of GJB2 235 site.

RESULTSTotally 16.3% of patients carried at least one 235 delC mutant allele. Among them, 7.8% was homozygous and 8.5% was heterozygous. The prevalence of GJB2 235delC mutation in China was evident, and the significant difference of 235delC mutation frequency was found in sub-population from different areas and different ethnic groups.

CONCLUSIONSBased upon the result of this screening as stated, Chinese NSHI patients appear to have 235delC frequency and the number of GJB2 related deafness was estimated to be huge. The testing of GJB2 235delC mutation would play an important role in genetic diagnosis and screening in China. As high as 15% of patients could be diagnosed as GJB2 caused deafness (bi-allelic mutation) only by means of this simple, fast and economic assay. In addition, patients were negative for 235delC mutation would be candidates for further mutational analysis of GJB2 or other deafness related genes.

Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; China ; epidemiology ; Connexin 26 ; Connexins ; genetics ; Female ; Genotype ; Hearing Loss, Sensorineural ; epidemiology ; genetics ; Heterozygote ; Homozygote ; Humans ; Male ; Point Mutation ; Prevalence ; Young Adult

Aedes ; virology ; Animals ; China ; epidemiology ; Genetic Variation ; Genome, Viral ; Humans ; Multigene Family ; Viral Proteins ; genetics ; Zika Virus ; classification ; genetics ; isolation & purification ; Zika Virus Infection ; epidemiology ; virology

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.